8-32547183-G-C

Variant names:

• chr8-32547183-G-C
• rs3802159
• ENST00000520407.5:c.746-48645G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000520407.5(NRG1):​c.746-48645G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,150 control chromosomes in the GnomAD database, including 2,083 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (2083 hom., cov: 32)
• Consequence: NRG1 ENST00000520407.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980
• Publications: 3 publications found

Genes affected

NRG1 (HGNC:7997): (neuregulin 1) The protein encoded by this gene is a membrane glycoprotein that mediates cell-cell signaling and plays a critical role in the growth and development of multiple organ systems. An extraordinary variety of different isoforms are produced from this gene through alternative promoter usage and splicing. These isoforms are expressed in a tissue-specific manner and differ significantly in their structure, and are classified as types I, II, III, IV, V and VI. Dysregulation of this gene has been linked to diseases such as cancer, schizophrenia, and bipolar disorder (BPD). [provided by RefSeq, Apr 2016]

NRG1 Gene-Disease associations (from GenCC):

• schizophrenia 6

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000520407.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG1	NM_001159999.3		c.38-48645G>C		intron	N/A	NP_001153471.1
	NRG1	NM_001159995.3		c.38-48645G>C		intron	N/A	NP_001153467.1
	NRG1	NM_001160001.3		c.38-48645G>C		intron	N/A	NP_001153473.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRG1	ENST00000520407.5	TSL:1	c.746-48645G>C		intron	N/A	ENSP00000434640.1
	NRG1	ENST00000523534.5	TSL:5	c.305-48645G>C		intron	N/A	ENSP00000429067.1
	NRG1	ENST00000650866.1		c.38-48645G>C		intron	N/A	ENSP00000499045.1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16250 AN: 152032 Hom.: 2072 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0887

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.0971

Gnomad FIN AF: 0.0344

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0233

Gnomad OTH AF: 0.0931

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.107 AC: 16281 AN: 152150 Hom.: 2083 Cov.: 32 AF XY: 0.110 AC XY: 8180 AN XY: 74388

African (AFR) AF: 0.221 AC: 9159 AN: 41472

American (AMR) AF: 0.0891 AC: 1362 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 83 AN: 3468

East Asian (EAS) AF: 0.594 AC: 3060 AN: 5150

South Asian (SAS) AF: 0.0966 AC: 466 AN: 4826

European-Finnish (FIN) AF: 0.0344 AC: 365 AN: 10596

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0233 AC: 1585 AN: 68028

Other (OTH) AF: 0.0907 AC: 192 AN: 2116

Alfa AF: 0.0654 Hom.: 103

Bravo AF: 0.120

Asia WGS AF: 0.256 AC: 890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.34
PhyloP100		-0.098
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3802159; hg19: chr8-32404701;